Improvement of severe secondary hyperparathyroidism in dialysis patients by intravenous 1 alpha(OH) vitamin D3, oral CaCO3 and low dialysate calcium.

Seventeen patients (9 men, 8 women; aged 27 to 75 years) who were on chronic hemodialysis for 1 to 14 years were included in the study because they had severe hyperparathyroidism diagnosed by elevated plasma alkaline phosphatase and on plasma intact PTH levels more than twice the upper limit of normal. They had been previously treated with various combinations of oral calcium and/or Al(OH)3 as phosphate binders, oral 1 alpha(OH) vitamin D3 metabolites and a dialysate calcium concentration (DCa) of 1.6 to 1.75 mmol/liter. When i.v. alpha calcidol was introduced DCa was reduced to 1.25 mmol/liter and CaCO3 taken with the meal was used as the sole phosphate binder. alpha calcidol was i.v. injected after the third dialysis of the week at a dose up to 4 micrograms per dialysis in order to obtain a predialysis plasma concentration of Ca at 2.5 +/- 0.2 and PO4 between 1.5 and 2 mmol/liter. All the other treatments were discontinued. During the six months of follow-up, the mean weekly dose of alpha calcidol was 6 micrograms and CaCO3 700 +/- 50 mmol. Plasma calcium (PCa) increased moderately from 2.35 to 2.47 mmol/liter (P < 0.05) whereas plasma PO4 (PPO4) did not significantly increase (1.56/1.64 mmol/liter). Total alkaline phosphatase and its bone isoenzyme activity decreased significantly to normal values [respectively from 186 to 83 IU (normal: 135) and from 102 to 32 IU (normal < 33)] whereas plasma intact PTH decreased from 485 to 125 pg/ml (normal < 55).(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-HLA antibodies depletion on protein A-sepharose columns in hyperimmunized patients awaiting renal transplantation.

To reduce anti-HLA immunization, 15 patients waiting for a renal graft received the following treatment: 5 to 7 immunoadsorption sessions on protein A-Sepharose columns, immunosuppressive drugs (corticosteroids 1 mg/kg (bw/day+cyclophosphamide 2 mg/kg bw/day) and iv polyclonal immunoglobulins. Before this treatment, panel-reactive antibodies ranged from 65 to 100% and antibody titers varied from 1/8 to 1/128. In all patients, antibody, titers were decreased. However, antibody resynthesis was incompletely blocked by this protocol. Eight out of 12 grafted patients had a functional kidney transplant 3 months to 3 years post-grafting. There early kidney failures occurred in the subgroup of 5 patients who had had historical positive cross matches prior to treatment. This treatment did not seem to increase the frequency of infectious complications before or after grafting.

[Treatment of cytomegalovirus infections with ganciclovir in kidney transplant recipients. Clinical and pharmacokinetic study]. / Traitement des infections à cytomégalovirus par le ganciclovir chez les transplantés rénaux. Etude clinique et pharmacocinétique.

Ganciclovir (DHPG) was used in 32 renal transplant recipients with proven cytomegalovirus (CMV) disease. Mean time of CMV occurrence from grafting was 49 days. CMV disease was recognized on the combination of both clinical signs and histological or virological findings. DHPG treatment, adapted to renal function was given for 14 days and a pharmacokinetic study was performed at days 1, 7 and 14. Twenty nine patients, 10 of whom has severe to moderate disease, were improved by treatment. Three patients died, 2 of them with severe pulmonary and hepatic diseases. Few adverse effects were observed (leucopenia: n = 7, thrombopenia: n = 2, abdominal pain: n = 1). CMV was no longer found in virological samples in 80 percent of the patients. Maximal plasma concentration of DHPG (9.3 +/- 0.3 micrograms/ml, m +/- SEM) was reached at the end of the one hour infusion and decreased according to a biexponential model. The half life of elimination was 3.35 +/- 0.32 hours, the metabolic clearance 128 +/- 7 ml/min and the distribution volume about 50 percent body weight (0.48 +/- 0.02 l/kg). The clearance of DHPG was greater than creatinine clearance, and was linearly correlated with it, suggesting that renal elimination was important, both by glomerular filtration and tubular secretion. These results indicate that DHPG is effective and well tolerated for the treatment of CMV disease in renal transplant recipients. Renal elimination of the drug requires dosage adjustment to renal function.

[Pharmacokinetic study of a cephalosporin: cefoperazone in patients with a Kehr drain]. / Etude pharmacocinétique d'une céphalosporine: la céfopérazone chez des patients porteurs d'un drain de Kehr.

Cefoperazone is a semi-synthetic cefalosporine for parenteral use which has an excellent activity against a wide range of grampositive and gramnegative bacteria, especially Pseudomonas aeruginosa, Enterobacter, Proteus indole positive and Serratia marcescens. The pharmacokinetics of the new antibiotic have been studied in patients who had undergone cholecystectomy and choledochotomy for lithiasis and who required T-tube drainage of the bile duct. Five patients were anicteric and one was icteric. Mean serum concentration of cefoperazone determined by a microbiological method) measured after a two-hour intravenous perfusion of 2 g cefoperazone was 198.6 microgram/lm; this level is higher than the mean level measured in normal subjects (134 microgram/ml) but lower than the mean level measured in patients with hepatic insufficiency (208 microgram/ml). Apparent half life of elimination was longer (mean 4.1 hours) in the patients than in controls (mean 1.6 hours) and compares with that of patients with hepatic insufficiency (mean 4.3 hours). The distribution volume and renal clearance are similar to that in healthy volunteers and patients with hepatic insufficiency. Extrarenal clearance of cefoperazone was significantly lower in our patients (15.8 ml/min), as it is in patients with hepatic insufficiency (7.3 ml/min), than in the control group (59.4) ml/min). Cefoperazone concentrations in the bile were 10-20 times higher than those in the serum; in the icteric patient the concentrations achieved were still higher than the MIC values for organisms commonly encountered in the bile. These results open the way to the use of cefoperazone to treat infectious biliary diseases, particularly angiocholitis, which need a high biliary antibiotic concentration.